Diabetic Cardiomyopathy: Cardiac Changes, Pathophysiological Mechanisms, Biologic Markers, and the Available Therapeutic Armamentarium

Patients with diabetes mellitus (DM) exhibit greatly increased cardiovascular morbidity and mortality. The increased mortality of patients with DM stems from the more frequent development of heart failure (HF) (Bell, 2003a; Jaffe et al., 1984; Kamalesh, 2007; Marwick, 2006; Solomon et al., 2002). In the past, the high incidence and poor prognosis of HF in diabetic patients was attributed to the concurrent presence of hypertension and/or myocardial ischemia. However, follow-up studies have shown that the increased risk for developing HF persists in DM patients even after adjusting for concomitant risks such as coronary artery disease and blood pressure (Ho et al., 1993; Kannel & McGee, 1979). It is now well established that DM increases the risk of cardiovascular morbidity and mortality by promoting cardiomyopathy, a distinct entity independent of coronary artery disease, hypertension or other known cardiac risk factors with origins in diabetic cardiac muscle (Bell, 1995; Cohen, 1995; Hamby et al., 1974; Regan et al., 1977; Spector, 1998). According to a new study commissioned by the Centers for Disease Control and Prevention, 25.8 million children and adults in the United States, or 8.3% of the population, have DM, with about 1.9 million new cases of DM being diagnosed annually (Centers for Disease Control and Prevention, 2011). Worldwide, the number of people with DM has more than doubled since 1980 to 347 million (Danaei et al., 2011). With the global burden of DM rising, it is likely that the incidence of diabetes-induced cardiomyopathy and subsequent HF will continue to increase in this high-risk population. The goal of this chapter is to review the structural and functional changes in the diabetic heart and the pathophysiological mechanisms involved in the development of diabetic cardiomyopathy, taking into account the most recent developments in basic and clinical research. An overview of the latest advances in therapeutic approaches to treat diabetic cardiomyopathy will also be presented. Particular attention is given to the role of oxidative stress in the pathogenesis of diabetic cardiomyopathy and the potential of anti-oxidative therapy. The value of newly identified candidate biomarker proteins in assessing disease presence and progression, prognosis, and efficacy of therapies in the setting of diabetic cardiomyopathy will also be discussed.